An adrenergic agonist is a
drug that stimulates a response from the
adrenergic receptors
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...
. The five main categories of adrenergic receptors are: α
1, α
2, β
1, β
2, and β
3, although there are more subtypes, and agonists vary in specificity between these receptors, and may be classified respectively. However, there are also other mechanisms of adrenergic agonism.
Epinephrine and
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...
are
endogenous and broad-spectrum. More selective agonists are more useful in pharmacology.
An ' agent is a
drug, or other substance, which has effects similar to, or the same as,
epinephrine (adrenaline). Thus, it is a kind of
sympathomimetic agent. Alternatively, it may refer to something which is susceptible to epinephrine, or similar substances, such as a biological
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
(specifically, the
adrenergic receptors).
Receptors
Directly acting adrenergic agonists act on adrenergic receptors. All adrenergic receptors are G-protein coupled, activating signal transduction pathways. The G-protein receptor can affect the function of
adenylate cyclase
Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction:
:A ...
or
phospholipase C, an agonist of the receptor will upregulate the effects on the downstream pathway (it will not necessarily upregulate the pathway itself).
The receptors are broadly grouped into α and β receptors. There are two subclasses of α-receptor, α
1 and α
2 which are further subdivided into α
1A, α
1B, α
1D, α
2A, α
2B and α
2C. The α
2C receptor has been reclassed from α
1C, due to its greater homology with the α
2 class, giving rise to the somewhat confusing nomenclature. The β receptors are divided into β
1, β
2 and β
3. The receptors are classed physiologically, though pharmacological selectivity for receptor subtypes exists and is important in the clinical application of adrenergic agonists (and, indeed, antagonists).
From an overall perspective, α
1 receptors activate
phospholipase
A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. Acids trigger the release of bound calcium from cellular stores and the consequent increase in free cytosolic Ca2+, an essential step in ...
C (via G
q), increasing the activity of
protein kinase C (PKC); α
2 receptors inhibit adenylate cyclase (via G
i), decreasing the activity of
protein kinase A
In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, including regulatio ...
(PKA); β receptors activate adenylate cyclase (via G
s), thus increasing the activity of PKA. Agonists of each class of receptor elicit these downstream responses.
Uptake and storage
Indirectly acting adrenergic agonists affect the uptake and storage mechanisms involved in adrenergic signalling.
Two uptake mechanisms exist for terminating the action of adrenergic catecholamines - uptake 1 and uptake 2. Uptake 1 occurs at the presynaptic nerve terminal to remove the neurotransmitter from the synapse. Uptake 2 occurs at postsynaptic and peripheral cells to prevent the neurotransmitter from diffusing laterally.
There is also enzymatic degradation of the catecholamines by two main enzymes -
monoamine oxidase and
catechol-o-methyl transferase
Catechol-''O''-methyltransferase (COMT; ) is one of several enzymes that degrade catecholamines (neurotransmitters such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol struct ...
. Respectively, these enzymes oxidise monoamines (including catecholamines) and methylate the hydroxyl groups of the phenyl moiety of catecholamines. These enzymes can be targeted pharmacologically. Inhibitors of these enzymes act as indirect agonists of adrenergic receptors as they prolong the action of catecholamines at the receptors.
Structure–activity relationship
In general, a primary or secondary aliphatic amine separated by 2 carbons from a substituted benzene ring is minimally required for high agonist activity.
Mechanisms
A great number of drugs are available which can affect adrenergic receptors.
Other drugs affect the uptake and storage mechanisms of adrenergic catecholamines, prolonging their action. The following headings provide some useful examples to illustrate the various ways in which drugs can enhance the effects of adrenergic receptors.
[Lippincott's Pharmacology 5th edition page 69-85]
Direct action
These drugs act directly on one or more adrenergic receptors. According to receptor selectivity they are two types:
*Non-selective: drugs act on one or more receptors; these are:
**
Adrenaline
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands an ...
(almost all adrenergic receptors).
**
Noradrenaline
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
(acts on α
1, α
2, β
1).
**
Isoprenaline
Isoprenaline, or isoproterenol (brand name: Isoprenaline Macure), is a medication used for the treatment of bradycardia (slow heart rate), heart block, and rarely for asthma. It is a non-selective β adrenoceptor agonist that is the isopropyla ...
(acts on β
1, β
2, β
3).
**
Dopamine (acts on α
1, α
2, β
1, D
1, D
2).
*Selective: drugs which act on a single receptor only; these are further classified into α selective & β selective.
** α
1 selective:
phenylephrine
Phenylephrine is a medication primarily used as a decongestant, to dilate the pupil, to increase blood pressure, and to relieve hemorrhoids. In the United States, it was previously used orally as an over-the-counter decongestant to relieve nas ...
,
methoxamine,
midodrine
Midodrine is a vasopressor/ antihypotensive agent (it raises the blood pressure). Midodrine was approved in the United States by the Food and Drug Administration (FDA) in 1996 for the treatment of dysautonomia and orthostatic hypotension. In A ...
,
oxymetazoline
Oxymetazoline, sold under the brand name Afrin among others, is a topical decongestant and vasoconstrictor medication. It is available over-the-counter as a nasal spray to treat nasal congestion and nosebleeds, as eyedrops to treat eye rednes ...
.
** α
2 selective:
α-methyldopa,
clonidine,
brimonidine,
dexmedetomidine
Dexmedetomidine, sold under the trade name Precedex among others, is a drug used in humans for sedation. Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses. It is also used in humans to treat acute agitation ...
.
** β
1 selective:
dobutamine
Dobutamine is a medication used in the treatment of cardiogenic shock (as a result of inadequate tissue perfusion) and severe heart failure. It may also be used in certain types of cardiac stress tests. It is given by IV only, as an injection in ...
.
** β
2 selective:
salbutamol/albuterol,
terbutaline
Terbutaline, sold under the brand names Bricanyl and Marex among others, is a β2 adrenergic receptor agonist, used as a "reliever" inhaler in the management of asthma symptoms and as a tocolytic (anti-contraction medication) to delay preterm ...
,
salmeterol
Salmeterol (sold in China as Qitai) is a long-acting β2 adrenergic receptor agonist (LABA) used in the maintenance and prevention of asthma symptoms and maintenance of chronic obstructive pulmonary disease (COPD) symptoms. Symptoms of bronchos ...
,
formoterol
Formoterol, also known as eformoterol, is a long-acting β2 agonist (LABA) used as a bronchodilator in the management of asthma and chronic obstructive pulmonary disease (COPD). Formoterol has an extended duration of action (up to 12 h) co ...
,
pirbuterol
Pirbuterol (trade name Maxair) is a short-acting β2 adrenoreceptor agonist with bronchodilating action used in the treatment of asthma, available (as pirbuterol acetate) as a breath-activated metered-dose inhaler.
It was patented in 1971 a ...
, clenbuterol.
Indirect action
These are agents that increase neurotransmission in endogenous chemicals, namely
epinephrine and
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...
.
Mixed action
*
Ephedrine
Ephedrine is a central nervous system (CNS) stimulant that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in ...
*
Pseudoephedrine
See also
*
Adrenergic receptor
*
Alpha adrenergic agonist
*
List of adrenergic drugs
This is a list of adrenergic drugs. These are pharmaceutical drugs, naturally occurring compounds and other chemicals that influence the function of the neurotransmitter epinephrine (adrenaline).
Receptor ligands α1-adrenergic receptor ligan ...
References
External links
Virtual Chembook article on adrenergic drugs*
{{DEFAULTSORT:Adrenergic Agonist
Endocrine system